Vermeulen 2012.

Methods	Study design: randomised, double‐blind, placebo controlled Duration: 6 months after the second vaccination
Participants	Inclusion criteria Setting: outpatient Country: 6 sites: USA (n = 5) and the Netherlands (n = 1) Number: 209 participants; treatment (N = 104), control (N = 105) Participants' health status: healthy participants with a history of varicella and no prior herpes zoster Age: mean 69.7 years Sex: more than 60% female Other relevant information: aged ≥ 60 years 97.1% Caucasian (understood to be white) Exclusion criteria "Previous vaccination with any VZV‐containing vaccine, exposure to varicella or HZ within 4 weeks prior to study initiation, immune deficiency associated with illness or medical treatments (e.g. corticosteroids), neoplastic disease, receipt of blood products for 3 months prior to the first study dose, hypersensitivity or anaphylactic reactions to gelatin or neomycin (ingredients of the ZV), used any non‐topical antiviral therapy, or received any inactivated or live vaccine 6 weeks prior to the first study dose or during the study."
Interventions	Treatment group Lyophilised live zoster vaccine (frozen) SC (˜ 23,000 pfu); N = 104 Control group Placebo SC; N = 105
Outcomes	Adverse events, both injection site and/or systemic. Swelling, redness, pain, or tenderness or rash at the injection site, or varicella(‐like) rash or herpes zoster(‐like) rash, any serious adverse events
Purpose of the study	"To examine the safety, tolerability and immunogenicity after 1 and 2 doses of zoster vaccine in adults 60 years of age and older"
Funding sources	Merck Sharp & Dohme Corp
Conflicts of interest	Carrie Freeman, Ira Chalikonda, Jianjun Li, Jeffrey G Smith, Michael J Caulfield, Jon E Stek, Ivan SF Chan, Rupert Vessey, Florian P Schödel, Paula W Annunziato, Katia Schlienger, and Jeffrey L Silber are employees of Merck Sharp & Dohme Corp., and all other authors have been investigators for the sponsor. Dr Levin is a consultant for Merck and shares intellectual property in the zoster vaccine. Employees may hold stock or stock options, or both, in the company.
Notes	The first and second doses were administered 42 days apart (post‐vaccination 1 and post‐vaccination 2). 1 participant in the vaccine group withdrew consent before vaccination. Discontinued after first vaccination (vaccine group): clinical AE = 3; withdrew consent = 1; no participants lost to follow‐up or due to protocol deviation; other = 2 Discontinued after first vaccination (placebo group): clinical AE = 1; withdrew consent = 1; no participants lost to follow‐up; protocol deviation = 1; other = 1 Discontinued after second vaccination (vaccine group): only 1 participant due to clinical AE Discontinued after second vaccination (placebo group): 1 lost to follow‐up and 2 for other reasons No ITT analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomised in a 1:1 ratio to receive 2 doses of either ZV or placebo, according to a computer‐generated, study‐centre specific allocation schedule"
Allocation concealment (selection bias)	Low risk	"Allocation numbers were assigned sequentially by the study site personnel to subjects who met the study eligibility criteria, beginning with the lowest number available at the study centre, after informed consent and medical history had been obtained. The allocation schedule was generated by a sponsor statistician not otherwise associated with the ZV program"
Blinding (performance bias and detection bias) All outcomes	Low risk	"The subject, investigator, clinical study site personnel, and sponsor personnel directly involved in the study were blinded to whether the subject received zoster vaccine or placebo. They remained blinded until all subjects completed the study"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The clinical materials were prepared by an unblinded vaccine coordinator at each clinical site, because of differences in the turbidity of the study vaccine and placebo. Each vial of vaccine or placebo was labelled with a subject‐specific allocation number. The unblended vaccine coordinator reconstituted the study vaccine/placebo and wrapped the syringe in an opaque label containing subject allocation number and time of reconstitution. The unblinded vaccine coordinator did not have any contact with the subject and did not disclose the contents of the syringe to the person administering the study vaccine/placebo"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Clear patient flow
Selective reporting (reporting bias)	Low risk	All adverse events prespecified by the authors were described in the results for both vaccinations.
Other bias	Unclear risk	Insufficient information